1 / 27

Sequence-Structure-Function

Sequence-Structure-Function. Sequence Structure Function. Folding: impossible but for the smallest structures. Ab initio. Threading. Function prediction from structure – very difficult. BLAST. Experimental. Structural genomics Functional genomics Protein-protein interaction

justin
Download Presentation

Sequence-Structure-Function

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Sequence-Structure-Function Sequence Structure Function Folding: impossible but for the smallest structures Ab initio Threading Function prediction from structure – very difficult BLAST

  2. Experimental • Structural genomics • Functional genomics • Protein-protein interaction • Metabolic pathways • Expression data

  3. Protein function groups • Catalysis (enzymes) • Binding – transport (active/passive) • Protein-DNA/RNA binding (e.g. histones, transcription factors) • Protein-protein interactions (e.g. antibody-lysozyme) • Protein-fatty acid binding (e.g. apolipoproteins) • Protein – small molecules (drug interaction, structure decoding) • Structural component (e.g. -crystallin) • Regulation • Signalling • Transcription regulation • Immune system • Motor proteins (actin/myosin)

  4. Energy difference upon binding Examples of protein interactions (and functional importance) include: • Protein – protein (pathway analysis); • Protein – small molecules (drug interaction, structure decoding); • Protein – peptides, DNA/RNA  (function analysis) The change in Gibb’s Free Energy of the protein-ligand binding interaction can be monitored and expressed by the following;  G =  H - T x S      (H=Enthalpy, S=Entropy and T=Temperature)

  5. Protein function • Many proteins combine functions • Some immunoglobulin structures are thought to have more than 100 different functions (and active/binding sites) • Alternative splicing can generate (partially) alternative structures

  6. Protein function Protein-protein interaction Active site / binding cleft Shape complementarity

  7. Protein function evolution Chymotrypsin

  8. How to infer function • Experiment • Deduction from sequence • Multiple sequence alignment – conservation patterns • Homology searching • Deduction from structure • Threading • Structure-structure comparison • Homology modelling

  9. Mevalonate plays a role in epithelial cancers: it can inhibit EGFR

  10. Metabolic networksGlycolysis and Gluconeogenesis Kegg database (Japan)

  11. Gene Ontology (GO) • Not a genome sequence database • Developing three structured, controlled vocabularies (ontologies) to describe gene products in terms of: • biological process • cellular component • molecular function in a species-independent manner

  12. The GO ontology

  13. Gene Ontology Members

More Related